MASS COMM Trial

A Randomized Trial to Compare Percutaneous Coronary Intervention between Massachusetts Hospitals With Cardiac Surgery On-Site and Community Hospitals Without Cardiac Surgery On-Site MASS COMM
Alice K. Jacobs, Sharon-Lise T. Normand, Joseph M. Massaro, Donald E. Cutlip, Joseph P. Carrozza, Anthony D. Marks, Nancy Murphy, Iyah K. Romm, Madeleine Biondolillo, Laura Mauri for the MASS COMM Investigators and Coordinators

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Disclosures
This study was funded by Massachusetts Hospitals without on-site cardiac surgery. There are no relevant RWI to disclose.

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Background
Emergency coronary artery bypass surgery (CABG) has become a rare event following percutaneous coronary intervention (PCI), with a reported incidence of 0.1-0.4% in contemporary series. As data supporting primary PCI for patients with STsegment elevation myocardial infarction (STEMI) have emerged, the need for timely access to the procedure has justified the expansion of emergency PCI to hospitals without on-site cardiac surgery, where reported outcomes have been favorable.

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Background
Yet, controversy exists over the further expansion of non-emergency PCI to hospitals without on-site cardiac surgery, due to concern over the risk to benefit ratio in a setting where timely access to PCI is less important for optimal cardiovascular outcomes, which is reflected in the Class IIb recommendation in the 2011 PCI guidelines. MASS COMM was designed in 2006, with the Massachusetts Department of Public Health (MA-DPH), to provide evidence on which to base regulatory policy decisions about performing non-emergency PCI in hospitals without on-site cardiac surgery.

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Aim
To determine the short-term safety and 12-month outcomes of PCI (excluding primary PCI for STEMI) performed at hospitals without in comparison to with on-site cardiac surgery in Massachusetts

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MASS COMM Design

Patients undergoing coronary angiography at hospital without onsite cardiac surgery Randomized 3:1 Stratified by Diabetes PCI at hospital without onsite surgery (n=10 sites) PCI at hospital with on-site surgery (n=7 sites)

Exclusion Criteria
left ventricular ejection fraction < 20% target lesions with: - unprotected left main stenosis >50% - device other than balloon angioplasty prior to stent - saphenous vein graft location - vessel serving only viable myocardium

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Methods
Design
- prospective, multicenter, randomized, controlled

non-inferiority trial
Co-Primary End Points - composite of all-cause mortality, myocardial infarction (MI),* repeat coronary revascularization or stroke (MACE) at 30-days (safety) and 12-months (effectiveness)
*Q wave or non-Q-wave; non-Q wave MI defined as CK twice ULN plus elevated CK-MB or CK-MB 3 times normal

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Methods
Secondary Outcomes
- included all-cause mortality, repeat revascularization, stroke,
ischemia-driven target vessel and target lesion revascularization; Academic Research Consortium (ARC) defined definite or probable stent thrombosis; emergency CABG; emergency or urgent PCI; and major vascular complications

Angiographic Subset
- random sample of 10% of enrolled patients, CEC blinded to treatment assignment assessed lesion and procedure success, complete revascularization, and the proportion of lesions meeting PCI guidelines Class I or II recommendations for anatomic indications to perform PCI

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Statistical Methods
Analysis
- primary end points were compared for non-inferiority assessed via the Farrington-Manning test using relative risk non-inferiority margins of 1.5 and 1.3, respectively; P value of less than 0.05 on both end points required to determine noninferiority overall; all other end points compared for differences

Sample Size
- 3,447 evaluable patients to yield 80% to 85% power for the 30day safety end point (expected MACE 6-7%) and 85% to 88% power for the 12-month effectiveness end point (expected MACE 15-16%) for both arms

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Statistical Methods
Analysis
- Formal non-inferiority testing on an intent-to-treat

basis (all randomized patients) - Patients missing the 12-month follow-up visit -> 99% of records successfully linked to mortality data from state vital statistic records - Multiple imputation used for patients with remaining missing information regarding MACE

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Hospital and Operator Requirements for Participation in MASS COMM

Hospitals without on-site cardiac surgery
- Approval from MA-DPH

- Formal PCI development program - Participation in MA-DPH special project for primary PCI - Signed Collaboration Agreement with on-site surgery hospital (24/7 back-up, patient arrival within 60 minutes) - Perform minimum 300 diagnostic procedures in each of previous 2 years; 36 primary PCI procedures/year

All Operators - Perform minimum 75 PCI procedures/year

- ABIM Interventional Cardiology Board Certification

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Patient Randomization and Follow-up

Patients undergoing coronary angiography at hospital without on-site cardiac surgery n=3691 PCI at hospital without onsite surgery n=2774 n=68 excluded n=2706 (97.5%) 30-day end point n=267 excluded n=2439 (87.9%) 12-month end point PCI at hospital with on-site surgery n=917 n=31 excluded n=886 (96.6%) 30-day end point n=99 excluded n=787 (85.8%) 12-month end point

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Baseline Characteristics
No On-Site Surgery On-Site Surgery (n 2774) (n=917) 64.711.8 64.211.8
31.8 91.1 31.7 60.0 33.6 92.9 32.2 60.5

Age, years Female Sex (%) Caucasian (%) Diabetes (%) Current or Former Smoker (%)

Heart Failure (%)

Stroke (%) PVD (%)

8.1
2.8 10.4

7.1
3.5 10.4

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Baseline Characteristics
No On-Site Surgery On-Site Surgery (n 2774) (n=917)
Prior PCI (%) 29.0 27.3

Prior CABG (%)

Prior MI (%)* Indication for PCI (%) NSTEMI Unstable Angina Stable Angina LVEF (%)
*P=0.015

5.4
24.1 19.0 44.8 27.0 55.410.3

7.0
20.2 17.1 46.8 28.1 56.09.7

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Angiographic Characteristics Site Reported

No On-Site Surgery (n=2774 patients, 4053 lesions) 1.170.40 1.470.77 2.990.56 15.128.73 85.6611.03 On-Site Surgery (n=917 patients, 1294 lesions) 1.170.41 1.430.70 2.920.49 14.847.95 85.2210.84

# vessels treated # lesions treated Ref. vessel diameter (mm)* Lesion length (mm) Pre % stenosis

Final % stenosis**
meanSD; *P<0.001, **P=0.005

2.4612.04

1.519.68

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Procedural Characteristics Site Reported

No On-Site Surgery (n=2774 patients, 4053 lesions) 83.3
98.8 32.6 63.7 2.2 0.61

Pre-TIMI 3 flow (%)* Final TIMI 3 flow (%)

On-Site Surgery (n=917 patients, 1294 lesions) 87.9

98.6 24.6 69.3 1.5 0.22

Type of stent (%)*

Bare Metal Drug-eluting Both Staged Procedure (%)
*P<0.001

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MACE at 30-Days (Safety)

No On-Site Surgery (n=2774) MACE (%) 9.5 On-Site Surgery (n=917) 9.4

Relative Risk 95% CI

1.00 (1.22)

P Value
<0.001

Components of 30-day endpoint (%) Death Myocardial Infarction Repeat Revascularization Stroke 0.7 6.5 2.7 0.4 0.3 6.5 3.5 0.1 1.96 (0.58-6.64) 1.01 (0.76-1.35) 0.77 (0.51-1.17) 3.93 (0.51-30.21) 0.44 1.00 0.25 0.21

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MACE at 12-Months (Effectiveness)

No On-Site Surgery (n=2774) MACE (%) 17.3 On-Site Surgery (n=917) 17.8

Relative Risk 95% CI

0.98 (1.13)

P Value
<0.001

Components of 12-month endpoint (%) Death Myocardial Infarction Repeat Revascularization Stroke 2.3 8.6 8.5 1.0 2.4 7.8 9.9 0.8 0.95 (0.57-1.60) 1.10 (0.84-1.45) 0.86 (0.67-1.11) 1.24 (0.51-3.04) 0.89 0.55 0.24 0.83

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Secondary End Points

No On-Site Surgery (n 2774) On-Site Surgery (n=917) 1.4 5.0 Relative Risk 95% CI 0.98 (0.51-1.88) 1.00 (0.70-1.43) P Value 1.00 1.00

Target-lesion revascularization (%)+

At 30 days At 12 months 1.3 4.9

Target-vessel revascularization (%)+

At 30 days
At 12 months Stent thrombosis (%) At 30 days At 12 months Major vascular complications at 30 days
+Ischemia-driven

1.5
5.6 0.6 1.1 1.5

1.5
5.4 0.8 2.1 1.5

1.03 (0.56-1.92)
1.05 (0.75-1.48) 0.75 (0.31-1.81) 0.55 (0.30-1.02) 1.04 (0.56-1.92)

1.00
0.86 0.48 0.07 1.00

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Procedural Characteristics in the Angiographic Cohort*

No On-Site On-Site Surgery Surgery (n=289 patients, (n=87 patients, 392 lesions) 106 lesions) Lesion success (%) 95.6 97.1 Relative Risk 95% CI 0.98 (0.951.02)

P Value
0.59

Procedural success (%)

Complete revascularization (%) Met indication criteria for PCI (%)

81.3
60.2 94.1

74.7
59.8 91.5

1.09 (0.951.24)
1.01 (0.831.23) 1.03 (0.971.10)

0.22
1.00 0.37

*Adjudicated by CEC blinded to treatment group

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Kaplan-Meier Curves for Freedom from MACE within 12-Months Post PCI Procedure

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Summary
In patients treated with non-emergency PCI performed in hospitals without in comparison to with on-site cardiac surgery in Massachusetts:

PCI was non-inferior with respect to MACE at 30-days (safety).

PCI was non-inferior with respect to MACE at 12-months (effectiveness).

There were no significant differences in all-cause mortality, MI, repeat revascularization, or stroke at 30days or 12-months.

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Limitations
While data were available in 97% of subjects at 30- days, data were not available for the 12-month follow-up visit in 13% of subjects. While the study inclusion criteria were broad, certain clinical and anatomic subsets were excluded, and thus, the findings in this study should not be extrapolated to these subgroups.

The study was powered to detect non-inferiority regarding the two co-primary composite end points but not the individual components, such as mortality or stroke.

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Conclusions
These data suggest that performance of PCI at hospitals without on-site cardiac surgery but with established programs and requisite hospital and operator procedural volume, may be considered an acceptable option for patients presenting to such hospitals for care.

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Acknowledgements
Participating Hospitals
Beth Israel Deaconess Hospital Boston Iniversity Medical Center Brigham and Womens Hospital Brockton Hospital Good Samaritan Medical Center Holy Family Hospital Lahey Clinic Lawrence General Hospital Lowell General Hospital Massachusetts General Hospital Melrose Wakefield Hospital Metro West Medical Center Norwood Hospital Saints Memorial Medical Center South Shore Hospital St. Elizabeths Medical Center Tufts Medical Center

Data Safety Monitoring Board

Frederick S. Ling, MD, Chair David R. Holmes, MD Harry Dauerman, MD Jennifer Gassman

Clinical Events Committee

Donald E. Cutlip, MD, Chair Paul Gordon, MD John Lopez, MD Robert Piana, MD

Data Analysis and Linkage

Harvard Clinical Research Institute Massachusetts Data Analysis Center

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MASS COMM Trial published online Monday, March 11,2013 NEJM.org